tbuckley/cabot-search huggingface dataset:
P1384: EFFECT OF NUTRITIONAL SUPPORT ON THE INCIDENCE OF MUCOSITIS IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION (AUTOHSCT) IN PATIENTS WITH HODGKIN’S LYMPHOMA. (INTERIM RESULTS)
Authors: S. Volchenkov, L. Filatova, T. Semiglazova, S. Lyubimov, I. Zyuzgin, I. Ishmatova, A. Zverkova, S. Elkhova, M. Motalkina, Y. Chudinovskikh, S. Shalaev, A. Koviazin
Journal: HemaSphere (2022)

Background: Correction of metabolic disorders is one of the important point’s supportive care during high-dosechemotherapy with autologous stem cell transplantation (autoHSCT) in patients with Hodgkin’s lymphoma (HL). The impact of nutritional support on recovery during autoHSCT for this group of patients is not clearly understood. To assess the effect of combined nutritional support on the frequency of mucositis, grade of mucositis, number of nasogastric tube in patients group, and frequency of blood transfusions during high-dose chemotherapy with autoHSCT in patients with HL. Aims: The study analyzed 68 patients with Hodgkin’s lymphoma who received high-dose chemotherapy with only parenteral nutritional support (NS) between 2013 and 2016 and 71 patients treated between 2016 and 2020 who received combined NS: combination of parenteral and enteral sipping nutrition. The primary endpoints were the frequency of mucositis, number of nasogastric tube in patients group. Methods: Group of patient without combined NS group received nutritional support using parenteral nutrition in case of a decrease in the level of total protein or albumin, which was assessed by a biochemical blood test. Patients in the combined nutritional support group received combined nutritional support with enteral sips in combination with parenteral nutrition, regardless of total protein and albumin levels. Results: The relative risk (RR) of developing stomatitis in the combined NS group was lower than in the group without combined NS: RR=0.67 (95% CI 0.49-0.92), p=0.015. Enteral nutritional support was associated with a reduced risk of stomatitis when adjusted for age, sex, and BMI: odds ratio (OR)=0.33, 95% CI 0.14-0.78, p=0.012. The RR of developing colitis in the combined NS group was lower: RR=0.58 (95% CI 0.36-0.94), p=0.026. Enteral nutritional support was associated with a reduced risk of colitis after adjusting for age, sex, and baseline BMI: OR=0.38, 95% CI 0.17-0.86, p=0.021. A nasogastric tube was placed statistically less frequently in the combined NS group: 3.0% (n=2) versus 19.6% (n=10), p=0.015. Enteral nutritional support was associated with a reduced frequency of nasogastric tube insertion when adjusted for age, sex, and baseline BMI: OR=0.16, 95%CI 0.03-0.83, p=0.029. In patients with an installed nasogastric tube, the duration of its stay did not statistically significantly differ between groups with and without combined NS: median 6 days (IQD: 4-8) vs. 5 days (IQD: 3-6), respectively (p=0.382). Summary/Conclusion: The data obtained show that combined nutritional support reduces the risk of mucositis, reduces the during frequency of nasogastric tube insertion autoHSCT in patients with Hodgkin’s lymphoma.
PB1866: RESPONSE TO NOVEL ANTI CD20 ANTIBODY AND BCL2 INHIBITOR IN A PATIENT WITH CLL AND MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS ASSOCIATED WITH LEUKEMIC KIDNEY INFILTRATION AND REVIEW OF LITERATURE
Authors: J. G. Goanta, I. Rotaru, C. I. Popa, A. M. Patrascu
Journal: HemaSphere (2022)

Background: Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder with mature B cell, characterized by a progressive accumulation of monoclonal B lymphocytes in the peripheral blood, bone marrow, lymphatic tissue and rarely in other organs. Although renal impairment occurs in approximately 80-90% of patients with CLL, nephrotic syndrome is rare and occurs in less than 2% of patients. In the literature this condition is reported in a maximum of 16 patients with CLL, and no cases described with Membranoproliferative glomerulonephritis (MPGN) treated with Obinutuzumab and Venetoclax. Renal failure due to leukemic infiltration in chronic lymphocytic leukemia is extremely rare condition. Aims: To evaluate the response of renal impairment due to leukemic infiltration and due to MPGN as well as disease response, after specific treatment, compared with literature data. Methods: We present a 58-year-old male diagnosed with B-CLL stage A (0) in November 2020, under hematologic regular monitoring with no specific therapy since November 2021. This year he presented with important lower and upper extremities edema, oliguria (1100ml / 24h), minor increase of lymph nodes and spleen; laboratory test showed: haemoglobin: 11.4 g / dl, white blood cells: 186.020 / mm3, platelet count 207.000 / mm3, urea: 126 mg / dl, creatinine: 1.94 mg / dl; urinary protein excretion: 10 g / 24 h, serum proteins: 4.7 g / dl, serum albumin: 1.9 g / dl. We contacted the Nephrology Department, where renal biopsy was performed with histopathological and immunohistochemical examination. Findings were consistent with MPGN secondary type and moderate involvement with leukemic cells CD20 +, CD5 +, CD23 +. Treatment with novel anti CD20 (cluster of differentiation) antibody Obinutuzumab and Venetoclax has been initiated with tumor lysis syndrome prophylaxis. Results: After first cycle of Obinutuzumab and Venetoclax (OV) regimen, renal function was normal, proteinuria has been improved decreasing to 1g / 24h, the edema was remitted and the blood count returned to normal, white blood cell count was 4.200 / mm3. Until today the patient followed 4 cycles of OV with complete remission of CLL and complete response of his underlying MPGN and leukemic renal infiltration. Summary/Conclusion: Of all the cases in the literature, our approach to this condition was different, choosing Obinutuzumab and Venetoclax therapy, obtaining the complete response after the first cycle.
PB2258: MANAGEMENT OF FEBRILE NEUTROPENIA IN LEUKEMIC PATIENTS: A MONOCENTRIC STUDY
Authors: W. Boufrikha, R. Rakez, Z. Mlayah, A. Cheffai, N. Slama, S. Boukhris, M. A. Laatiri
Journal: HemaSphere (2022)

Background: Febrile neutropenia (FN) is one of the major complications of chemotherapy, which requires urgent broad-spectrum antibiotics in order to minimise the high rate of morbidity and mortality. Aims: The aims of our study are to describe the demographic characteristics of febrile neutropenic episodes in leukemic patients and to evaluate the antibiotic prescriptions. Methods: This is a retrospective study conducted at the Haematology Department of Monastir, Tunisia, from January 2020 to December 2020. We included patients hospitalized for acute leukaemia treatment (induction or consolidation course) complicated by febrile neutropenia. Results: The twenty-six patients enrolled in the study were classified as high risk according to the Multinational Association of Supportive Care in Cancer (MASCC) score. Eighty-two febrile neutropenic episodes were studied. The median age of our population was 31 years (3-58 years) with a slight male predominance (sex-ratio: 1,16). The most frequent malignancy was acute myeloid leukaemia. In our study, 14 patients (53,8%) had at least 2 febrile neutropenic episodes and only 4 patients (15,4%) presented with one febrile episode. Fever of unknown origin (FUO) and clinically documented infection were found respectively in 36,6% and 28% of cases. Microbiologically documented infections (MDI) were noted in 29 cases of which 90% were monomicrobiol blood stream infections (BSI). Gram-positive Bacteria accounted for 75% of the isolated strains, Coagulase-negative Staphylococci (87,5%) being the most frequent. Gram-negative Bacteria were isolated in 25% of all strains with predominance of Escherichia coli (75%). Neither extended-spectrum beta-lactamases nor carbapenemase-producing microorganisms were detected (table 2). Table 2: - Characteristics of blood stream infections N % Blood stream infections 29 35.4 Monomicrobiol BSI 26 90 Polymicrobiol BSI (2 organisms) 3 10 Isolated organisms 32 100 è Gram-positive Bacteria 24 75 Coagulase-negative Staphylococci 21 87.5 Enterococcus faecium 2 8.4 Streptococcus pneumoniae 1 4.1 è Gram-negative Bacteria 8 25 Escherichia coli 6 75 Proteus mirabilis 1 12.5 Pseudomonas aeruginosa 1 12.5 *BSI: Blood stream infection Empirical antibiotic therapy was appropriate according to the European Conference on Infection in Leukaemia (ECIL) and the Infectious Diseases Society of America (IDSA) guidelines in 61% of cases. Favorable response to first-line antibiotherapy was seen in 74,4% of cases. Septic shock complicated the course of 2 MDI due to Coagulase-negative Staphylococci. Summary/Conclusion: FN in leukemic patients is an emergency and the onset of treatment should, in no way, be delayed. Demographic characteristics of our study consist with those reported in the literature and therapeutic prescriptions are in agreement with the international guidelines.
PB2293: HARNESSING ACCELERATED SEQUENTIAL EVANS SYNDROME
Authors: M. Almakadi, D. Aldhafeeri
Journal: HemaSphere (2022)

Background: Evan’s syndrome (ES) is a rare autoimmune disorder characterized majorly by the co-occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) with or without immune neutropenia. The ITP and AIHA commonly develop simultaneously, or sequentially within at least 8 months apart. The exact mechanism remains unclear; however, it is crucial to rule out secondary causes when formulating treatment plan. ES tends to be less responsive to therapy than isolated ITP or AIHA, and is usually associated with multiple relapses. Here we present a rare case of “accelerated” sequential ES. Aims: To outline the features of a unique time course of sequential ES, and how early novel therapy can lead to better outcome. Methods: Our 65-year-old male patient developed petechiae and wet purpura due to severe thrombocytopenia (platelets count 2 x109/L). ITP was suspected, and secondary causes were ruled out. He was refractory to corticosteroids and gamma globulins (Figuresolid curves). On Day 21, he developed severe neutropenia with a nadir of 0.1 x109 g/L and was initiated on granulocytes-colony stimulating factor (data not shown), which triggered the diagnosis of ES. He was started on romiplostim, that was escalated weekly (Figuresolid curves). He subsequently developed severe autoimmune hemolytic anemia with hemoglobin nadir of 49 g/L almost 6 weeks into his presentation. Corticosteroids’ dose was increased, and rituximab at 375 mg/m2 was added. It is interesting to note that both ITP and autoimmune neutropenia began to recover as the AIHA was progressing (Figure solid curves). Expectedly, our patient relapsed with ITP seven years later (Figure dashed curves). All secondary causes were ruled out, again. This prompted early initiation of romiplostim and rituximab. The patient did not develop autoimmune neutropenia and AIHA at his relapse. Unfortunately, he suffered gastrointestinal and intracranial bleedings that were managed conservatively. The ITP began to recover around 8 days earlier than initial presentation (Figure dashed curves). Results: Learning from our patient’s initial presentation, the strategy we adopted at relapse “harnessed” this patient’s ES triad by preventing the development of autoimmune neutropenia and AIHA, and shorted the time to platelets recovery, which we believe was delayed due to bleeding occurrences that will usually lead to platelets consumption. Image:Summary/Conclusion: ES results in variable cellular compromises with heterogenous time courses. It is associated with poorer response to therapy than isolated ITP, AIHA, or autoimmune neutropenia, which results in worse morbidity and mortality. Our case exhibits a very rare phenotype of accelerated sequential ES with corticosteroids refractoriness that was managed successfully with early addition of romiplostim and rituximab. The lack of response to corticosteroids shall induce introduction of novel therapies sooner in the treatment course of suspected ES cases.
PB2022: EXPLORING ALTERNATIVE DOSING REGIMENS OF SINGLE-AGENT BELANTAMAB MAFODOTIN ON SAFETY AND EFFICACY IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA: DREAMM-14
Authors: M. Hultcrantz, D. Kleinman, P. Ghataorhe, A. Mckeown, W. He, T. Ling, R. C. Jewell, J. Byrne, L. Eliason, E. Scott, J. Opalinska
Journal: HemaSphere (2022)

Background: Belantamab mafodotin (belamaf: BLENREP) is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC). In the DREAMM-2 study, belamaf showed deep responses with a manageable safety profile in patients with relapsed/refractory multiple myeloma (RRMM). At 13 months of follow-up, the median duration of response was 11 months and overall survival was 13.7 months at the 2.5 mg/kg Q3W dose. Corneal events are common and expected with belamaf and other MMAF-containing ADCs. In DREAMM-2, corneal events were managed with dose modifications. Clinical responses were observed even with prolonged dose holds, suggesting alternative dosing regimens may lower corneal event rates without compromising efficacy. Aims: The DREAMM-14 study (NCT05064358) will investigate if an improved benefit/risk profile of single-agent belamaf can be achieved by modifying the dose, schedule, or both, relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, randomized, open-label study will include adults with RRMM who had ≥3 prior lines of therapy (LOT), including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor. Patients with corneal epithelial disease (except nonconfluent superficial punctate keratitis) or with prior exposure to BCMA-targeted therapies, or ADCs will be excluded. Patients will be randomized into Arms A–D (n=40 each) and Arm E (n=20) in parallel and stratified by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4). Belamaf will be administered as follows—Arm A: 2.5 mg/kg Q3W; Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index), and visual acuity (Snellen chart or equivalent) in addition to corneal findings assessed by an eye care specialist. Patients in all Arms will have response assessments, safety assessments, and ophthalmic exams performed by an eye care specialist Q3W regardless of dosing schedule. Ocular event-related dose modifications (except in Arm E) will be guided by a modified Keratopathy and Visual Acuity scale. The primary endpoint will be incidence of ocular events. Key secondary endpoints include ocular safety and tolerability, overall safety and tolerability, pharmacokinetics, and efficacy outcomes. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Results: N/A Summary/Conclusion: First patient first visit is currently targeted for 04Mar22.
Covid-19: How has the pandemic differed across the four UK nations?
Authors: Sarah Scobie
Journal: BMJ (2022)

And can that tell us anything about the relative effectiveness of the varying restrictions and guidance they put in place? The Nuffield Trust's Sarah Scobie analyses the data We examined trends over the first two years of the pandemic in terms of the proportion of the population with covid-19 (from the Office for National Statistics' infection survey), people in hospital with covid per head of population, and the number of deaths registered with covid-19 mentioned on the death certificate per head of population (see box 1 for sources). Box 1 ### Data notes and sourcesRETURN TO TEXT
P1656: EVALUATION OF PLATELET FUNCTION IN RARE OR UNDIAGNOSED BLEEDING DISORDERS
Authors: P. Acuña Butta, E. Monzón Manzano, E. García Arias-Salgado, E. García Pérez, M. T. Álvarez Román, M. Martín Salces, M. I. Rivas Pollmar, A. dos Santos, V. Jimenez Yuste, N. V. Butta Coll
Journal: HemaSphere (2022)

Background: Qualitative and/or quantitative platelet defects promote bleeding and its identification requires a careful clinical evaluation and a rational use of diagnostic laboratory assays. Aims: To study platelet function by different methods in patients with hemorrhagic symptoms who are suspected of thrombopathy to compare results obtained with each system and validate usefulness of methods employed. Methods: We included 72 patients with bleeding suspected of thrombopathy, which in some cases was confirmed by genetic study (Table 1). Patients with coagulation disorders were excluded. We used the following methods to test platelet function: Light aggregometry in platelet-rich plasma (PRP) using ADP, collagen, epinephrine and arachidonic acid as stimulating agonists. Flow cytometry in PRP using TRAP and ADP to induce platelet activation, and PAC1 monoclonal antibody (mAb) to recognize activated fibrinogen receptor, and anti P- selectin and anti-CD63 mAbs to test, respectively, release from alpha and dense granules. PFA-100 ® in whole citrated blood with collagen +ADP and collagen+Epinephrine cartridges. Total Thrombus-formation Analysis System (T-TAS ® 01, Zarcos, Japan) with T-TAS ® PL-chip (capillaries covered with collagen / under flow) in blood samples drawn in BAPA, a potent synthetic anticoagulant which inhibits Factor Xa and thrombin. Results: Some bleeding due to platelet dysfunction was diagnosed by any of the methods used, but others can only be detected with some of the techniques tested (Table 2). This difference in the sensitivity of the methods may be due to the different experimental conditions used in each of them: type of sample used, platelets’ activators, and flow vs static conditions. Forty % of undiagnosed bleedings did not seem to be related to platelet dysfunction. Image:Summary/Conclusion: All methods are complementary and their sensitivity depends on the pathway evaluated by the technique used and the mechanism involved in platelet dysfunction.
P878: HIGH MUTATIONAL BURDEN OF CHROMATIN MODIFYING GENES DEFINES A RELATIVELY INDOLENT SUBGROUP OF PLASMA CELL DYSCRASIAS
Authors: X. Wang, B. Qiao, Y. Yu, J. Xu, L. Zuo, J. Chen, H. Cai, H. Han, X.-X. Cao, C. Sun, J. Li
Journal: HemaSphere (2022)

Background: Plasma cell dyscrasias (PCDs), including multiple myeloma (MM), light chain amyloidosis (AL), POEMS syndrome, and MGUS, present different clinical features. But as malignancies of plasma cells, they potentially have common mutational patterns associated with chemotherapy and prognosis, which haven’t been elucidated. Aims: We aimed to reveal the clinically relevant subgroups of MM, AL, POEMS, and MGUS defined by mutational patterns of bone marrow plasma cells (BMPCs). Methods: We conducted targeted gene sequencing including 370 genes of BMPCs from patients with MM (n=163), AL (n=121), POEMS (n=67) and MGUS (n=13). All the subjects provided informed consent. Results: Principal component analysis of the top 100 variable genes revealed 2 major subgroups among patients with PCDs (Fig. 1a). Approximately 25% of MM, AL, POEMS and MGUS, subgroup 1 was featured by the heavily mutated genes enriched in histone modifications and chromatin organization, such as KMT2D, EP400, RUNX1, SOX9, KDM5A, NCOR2, and ARID1B. Subgroup2 showed lower total mutational burden and was featured by mutations of proto-oncogene and B cell differentiation-associated genes, such as NCOR1, APOBEC4, KRAS, TP53, FGFR3, FAM46C, and MYC (Fig. 1b). The high mutational burden of chromatin-modifying genes was exclusively observed in subgroup 1 and was comparable among MM, AL, POEMS, and MGUS (Fig. 1c). Patients in subgroup 1 showed worse responses to the first-line CyBorD for MM and AL (Fig. 1d), but better responses to the lenalidomide-based VRD for MM and Rd for POEMS. Overall, patients in subgroup 1 demonstrated longer progression-free survival (PFS), which was observed in MM, AL (Mayo12, Stage I, II), and POEMS, respectively (Fig. 1e). Image:Summary/Conclusion: These results provide mechanistic insights into a relatively indolent subgroup among patients with MM, AL, POEMS, and MGUS, which is featured by a high mutational burden of chromatin-modifying genes. This subgroup can be identified by detecting the mutations of chromatin-modifying genes in clinical management. Overall longer PFS and better response to lenalidomide-based first-line therapy can be expected.
PB1882: RICHTER TRANSFORMATION FEATURES, SURVIVAL AND TREATMENT OUTCOME IN HEMATOLOGY CLINIC OF CRAIOVA, ROMANIA
Authors: I. Rotaru, L. Ocroteala, D. Duta, J. G. Goanta, A. M. Patrascu, C. I. Popa
Journal: HemaSphere (2022)

Background: Richter transformation is a rare but potential lethal complication in patients diagnosed with chronic limphocytic leukemia. The most common histological transformation is of Hodgkin lymphoma or Diffuse Large B-cell lymphoma type. Aims: The aim is to assess the clinicopathological characteristics survival and treatment in Richter transformation patients diagnosed and treated in Hematology Clinic of Craiova in the last 10 years. Methods: Between January 2012 and January 2022, 453 patients with chronic lymphocytic leukemia (CLL) were diagnosed and treated in our clinic, 121 female and 332 male. Results: Median age of the patients was 68 years and the male:female ratio was 2,74. The majority were diagnosed in A stage (52%), 27% in B stage and 21% in C stage. 29% of patients required treatment initiation upon diagnosis. Richter transformation occurs in 1,76 % cases (8/453) of all CLL. The transformation occurred as follows: 5 diffuse large B-cell lymphoma (DLBCL)-type pacients and 3 Hodgkin lymphoma-type pacients. In all cases the mutational status was unmutated, CD38 was positive in 6 patients and 3 patients were positive for TP53 mutation. The time until transformation lasted between 6 and 42 months, measured from treatment initiation. In 6 patients, transformation involved peripheral lymphadenopathy and in 2 patients, intraabdominal lymphadenopathy. The treatment received was ABVD regimen in Hodgkin transformation and R CHOP in DLBCL-type. On average, survival was 16 months in Hodgkin transformation and 7,8 months in DLBCL transformation. Summary/Conclusion: The Richter transformation is a rare complication of CLL, an indolent lymphoproliferative disorder. Only 8 patients were diagnosed with Richter transformation in our clinic in the last 10 years. Chemotherapy response was poor and survival was short.